Download Prurigo nodularis due to Mycobacterium tuberculosis

Journal of Medical Microbiology (2009), 58, 1649–1651
Case Report
DOI 10.1099/jmm.0.007518-0
Prurigo nodularis due to Mycobacterium
tuberculosis
Laura Saporito,1 Ada Maria Florena,2 Claudia Colomba,1
Diego Pampinella1 and Paola Di Carlo1
1
Correspondence
Infectious Diseases Section, Department of Health Promotion Sciences, University of Palermo,
Via del Vespro 129, 90127 Palermo, Italy
Paola Di Carlo
[email protected]
2
Department of Human Pathology, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy
Received 10 November 2008
Accepted 5 August 2009
Prurigo nodularis (PN) is a rare chronic skin disorder of unknown origin. Here we describe what is
believed to be the first case of PN associated with tuberculosis. For the first time, culture and PCR
analysis of skin biopsy confirmed the presence of Mycobacterium tuberculosis complex in PN skin
lesions. The pruritus and skin lesions resolved following antitubercular therapy. Our case provides
further evidence in favour of a link between PN and mycobacterial infection.
Introduction
Prurigo nodularis (PN) is a chronic skin disorder characterized by intensely pruritic papulonodular lesions that mainly
appear on the extensor surfaces of the limbs. The disease is
relatively rare and can occur at any age, but it is more
commonly reported in middle-aged women. The definition
and pathogenesis of PN are somewhat confusing. It is
described as being associated with a number of disorders.
Numerous infectious agents (bacterial and viral) have been
suggested as possible triggers. Although several studies have
provided important information linking infectious agents to
PN, strong evidence for a direct casual association between
such infections and PN is still lacking (Mattila et al., 1996;
Neri et al., 1998, 1999; Alfadley et al., 2003; Loffeld & Tan,
2004).
In some cases PN would appear to be the direct result of skin
infection, with the infectious organisms identifiable in skin
lesions, while in others (e.g. human immunodeficiency virus
and viral hepatitis) the lesions are apparently immunesystem mediated (Lee & Shumack, 2005; Accioly-Filho et al.,
2000). These observations suggest that it is simply a
common skin response to a variety of insults. PN is
consequently a difficult condition to treat and identifying a
treatment strategy can be challenging. To contribute to a
better understanding of this skin disorder, we report for
what is believed to be the first time a case of PN linked with
Mycobacterium tuberculosis complex (MTBC) infection in a
patient with pulmonary tuberculosis.
Case report
In July 2007, a 30-year-old man of Ghanaian origin came
to the Emergency Department of Policlinico ‘Paolo
Abbreviations: EIB, erythema induratum of Bazin; MTBC, Mycobacterium
tuberculosis complex; PN, prurigo nodularis.
007518 G 2009 SGM
Giaccone’ University Hospital, Palermo, Italy, with fever
and chest pain that he had been experiencing for 3 weeks.
The patient had lived in Italy for 5 years. A review of his
medical history revealed no signs of previous chronic
diseases. A human immunodeficiency virus test performed
on admission was negative.
At the time of admission, the patient was febrile (38.3 uC),
and complained of a productive cough and chest pain in
his left side. He was also experiencing intense itching in his
upper and lower limbs. On chest auscultation, localized
crackles and wheezing were heard in the left upper zone.
Further examination revealed nodular skin lesions 0.5–
1.5 cm in diameter, mainly on his upper and lower limbs.
The lesions were hard, hyperpigmented nodules, with a
smooth surface. Some of these nodules showed scratch
injury. The skin between the lesions was normal (Fig. 1).
The patient had suffered from these lesions for 15 months.
Laboratory tests revealed: a white blood cell count of 4180
cells mm23, with 49.3 % neutrophils, 27.5 % lymphocytes,
20.6 % monocytes and 1.9 % eosinophils; a haemoglobin
level of 11.7 g dl21; a platelet count of 145 000 cells mm23;
an aspartate aminotransferase level of 67 IU l21 and an
alanine aminotransferase level of 39 IU l21. Serum protein
electrophoresis revealed a slightly low level of albumin
(3.36 g dl21, normal range 3.48–5.39 g dl21) with
polyclonal hypergammaglobulinaemia (2.29 g dl21, normal range 0.67–1.56 g dl21). His blood glucose level, serum
electrolyte concentrations and renal function test results
were within normal limits.
A chest X-ray showed a bilateral parenchymal hilar and
peri-hilar consolidation, with marked interstitial bronchovascular fibrosis and bronchiectasiae in the left lung.
Thoracic computed tomography images confirmed the
presence of multiple bilateral areas of air space consolidation with small nodular lesions and cavitation. Fibrocalcific
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1649
L. Saporito and others
was negative. IS6110-PCR was carried out after extraction
of DNA using a protocol based upon incubation steps with
SDS and proteinase K, a phenol/chloroform extraction and
an RNase treatment. Checking for contaminant DNA was
performed using PCR amplification of a blank extract and
the PCR reagent mix. PCR yielded a positive result for
MTBC (Forbes & Hicks, 1993). Culture on Lowenstein–
Jensen medium was also positive for MTBC. Reported
methods were used to identify tubercle bacilli on colonies
obtained from cutaneous specimens (Roberts et al., 1991;
Lee et al., 2000).
Fig. 1. Hyperpigmented nodular lesions on the flexor surface of
the right forearm.
nodules were present in the upper region of the left lung.
Hilar-mediastinal lymphadenopathy was also detected.
The patient had a positive Mantoux skin test reaction
(12 mm in duration after 48 h). Acid-fast bacilli were
detected in a Ziehl–Neelsen-stained sputum smear. PCR
based on the amplification of the IS6110 insertion
sequence, followed by a hybridization step, was carried
out on the sputum sample and yielded a positive result for
MTBC (Forbes & Hicks, 1993). Sputum culture on
Lowenstein–Jensen medium was positive for acid-fast
bacilli that were identified as MTBC based on cultural
characteristics and biochemical tests (Roberts et al., 1991),
and on RFLP of the rpoB gene (Lee et al., 2000).
Pulmonary tuberculosis was diagnosed and the patient was
treated with quadruple therapy (rifampicin, isoniazid,
pyrazinamide and ethambutol) until susceptibility testing
results were available. Three weeks later, the result of
susceptibility test showed resistance to ethambutol. Due to
the patient’s poor compliance we decided to protract the
quadruple therapy, replacing ethambutol with intramuscular streptomycin for 30 days.
Six days after initiating antitubercular therapy a biopsy of
one of the nodules on the forearm was performed. A
clinical diagnosis of PN was made on the basis of
cutaneous features. An antihistaminic drug was administered for 15 days without any remission of symptoms.
Histological examination of the biopsy specimen showed
hyperparakeratosis, hypergranulosis (i.e. thickening of the
stratum granulosum) and acanthosis. Papillary dermal
sclerosis due to fibroblast hyperplasia along with a scant
perivascular lymphocytic infiltrate were also present; the
subcutaneous fat was not involved and no specific changes
related to tuberculosis were observed. These findings
confirmed the clinical suspicion of PN.
A fragment of the fresh biopsy sample was also examined
for the presence of mycobacteria. Ziehl–Neelsen staining
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Haematochemical parameters and sputum smears were
examined monthly. The only remarkable alteration was
seen in eosinophil number. This count was initially normal
(,300 cells mm23) but increased 2 weeks after admission,
reaching a peak of 579 cells mm23 1 month later.
About 40 days after beginning antitubercular therapy, the
patient reported an improvement in pruritus. After 2
months of treatment, a sputum smear was negative, and
the patient was discharged and referred for outpatient
follow up. At that time, the pruritus had disappeared and
the nodular lesions were still present though reduced in
size.
During the follow up, MTBC continued to be undetectable
in sputum samples examined with Ziehl–Neelsen staining,
and PCR was negative after 4 months of antitubercular
treatment. At that time, only a few small, non-itchy lesions
were still detectable on the patient’s limbs; his eosinophil
count was within the normal range. The patient completed
a standard 6 month course of antitubercular therapy.
Discussion
PN is one of the most challenging of all chronic skin
disorders in terms of establishing its aetiology and
determining treatment strategies (Accioly-Filho et al.,
2000; Alfadley et al., 2003). These issues are related to
what triggers it, as an important first step in therapy is to
identify the underlying cause and treat the condition
accordingly. Mattila et al. (1996) described six patients
affected by PN due to mycobacteria other than tuberculosis, identified by culture of skin biopsy specimens. Two
of these patients had a good response to treatment with
antitubercular drugs.
PN is a distinctive condition and its diagnosis is mainly
clinical (Accioly-Filho et al., 2000). For our patient, a
diagnosis of PN was made based on skin manifestations
and an intense itching that had led to the lesions rapidly
becoming excoriated or crusted.
Clinical and instrumental assessment associated with the
results of bacterial isolation from the lesions and the early
improvement of our patient’s symptoms following standard antitubercular therapy prompted us to assert that this
was, to the best of our knowledge, the first reported case of
PN linked to MTBC. Indeed, a relapse of skin lesions
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Journal of Medical Microbiology 58
Prurigo nodularis and tuberculosis
occurred during the active tuberculosis infection, and
improvement was evident after 40 days of effective
antitubercular therapy. Interestingly, the clinical remission
of skin lesions coincided with the negativization of
microbiological markers of systemic infection.
gations for MTBC (e.g. PCR and/or culture) combined
with histopathological analysis of PN lesions in patients
with risk factors associated with latent or active tuberculosis.
In the differential diagnosis of our patient we considered
erythema induratum of Bazin (EIB), also called tuberculids. EIB is a subcutaneous panniculitis and vasculitis,
which occurs mainly on the lower extremities of middleaged women with signs of vascular insufficiency. Like other
forms of cutaneous tuberculosis, it is considered to be a
hypersensitivity immune reaction to MTBC and biopsy
culture is always negative. Similar to our patient,
symptoms associated with EIB can improve with antitubercular therapy (Mascaró & Baselga, 2008; Segura et al.,
2008). Nevertheless, unlike in our patient’s case, EIB
lesions are not pruritic but painful, and the nodules are
confluent and erythematic, whereas in PN lesions the
nodules are rarely erythematic and, when erythema is
reported, it is in a precocious phase as the nodules rapidly
become pigmented (Accioly-Filho et al., 2000).
Furthermore, histological examination of biopsy specimens
obtained from our patient did not reveal any of the typical
features described in patients with EIB, but rather showed
the characteristic changes in epidermis and derma
consistent with PN (Segura et al., 2008; Lee & Shumack,
2005; Mobini et al., 2005).
Acknowledgements
It has been suggested that eosinophils play a pathogenic
role in PN (Accioly-Filho et al., 2000; Tanaka et al., 1995).
In our patient, the number of circulating eosinophils
increased during the course of antitubercular therapy.
Conversely, there was no increase in number of eosinophils
in the affected skin. We assumed that blood eosinophilia
was a drug-induced side effect, as reported by Wong et al.
(1995).
Cutaneous tuberculosis can be acquired either exogenously
(directly through injured skin) or endogenously (spreading
from other organs). Skin trauma due to scratching easily
introduces pathogens into the skin. However, in our case
the positive response to antitubercular therapy suggested
that M. tuberculosis spreading from the pulmonary
infection might have been the primary cause of the skin
disorder.
These findings suggest the need to consider a tubercular
aetiology for atypical chronic skin manifestations such as
PN, especially in patients coming from tuberculosisendemic countries, as systemic infection could be concomitant. Early diagnosis could prevent the development
of a more severe clinical picture.
In conclusion, this is believed to be the first documented
report of PN due to MTBC. Two recommendations arise
from our case: (i) it is opportune to consider PN as one of
the various patterns of cutaneous tuberculosis; (ii) it is
important to carry out specific microbiological investi-
http://jmm.sgmjournals.org
Our thanks to Professor Caterina Mammina, Department of Health
Promotion Sciences, University of Palermo, Italy, for providing
technical assistance.
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